Prevention of infections and treatment need in chronic lymphocytic leukemia with short-term combined venetoclax and acalabrutinib treatment.

Many patients with chronic lymphocytic leukemia (CLL) have a weakened immune system due to their disease. Thus, these patients have an increased risk of infections, which in worst case can be fatal. Severe CLL infections are responsible for one third of all deaths among CLL patients.

The purpose of the PreVent-ACaLL trial (ClinicalTrials.gov Identifier: NCT03868722) is to investigate whether a combination of two known types of cancer medicine (acalabrutinib and venetoclax) can reduce the risk of infection and thus mortality when given prophylactically to newly diagnosed CLL patients with a high risk of infection and/or early chemotherapy treatment.

Using the newly developed machine learning-based computer model CLL-TIM (CLL Treatment Infection Model, algorithm developed internally, Agius et al., Nature Communications, 2020), it can be predicted which patients are at high risk of developing infections as a result of their CLL over time. The aim is to initiate a preventive treatment in the period before the patients need chemoimmunotherapy. In this way, the cancer may be "reset" so the immune system, which is inhibited by CLL, is re-established and the risk of fatal infections is minimized. Participants are included from 7 sites, all hematology departments, in 3 different countries (Denmark, Sweden and the Netherlands). Participants are recruited within one year of diagnosis of CLL at the participating departments of hematology. Data are collected from patients with prediction of both high and low risk of infections.

The project has received support from the Novo Nordisk Foundation, AstraZeneca and AbbVie.

For further information please contact principal investigator Carsten Utoft Niemann, MD, PhD, carsten.utoft.niemann@regionh.dk or chip-prevent.rigshospitalet@regionh.dk.